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Linking Mass Spectrometry and Genetics for Studying the Various Biological Roles of Lipids
Linke, Vanessa ProQuest Dissertations & Theses The University of 2020 해외박사(DDOD)
Mass spectrometry (MS) provides access to the quantities and identities of biomolecular actors, including in the emerging field of lipidomics. While not genetically encoded, lipids are influenced by the genome through complex metabolic networks. This dissertation isconcerned with the connection of MS to genomic data to further the understanding of various metabolic phenomena ranging from an investigation of the molecular basis of the microbe-host interaction to the genetic causes of diabetes and obesity. Chapter 1 introduces these topics by giving an overview of the variety and functions of molecules acting in mammalian organisms, and the details of MS as a tool to measure their levels. Just as diverse as the biological questions are the technological ways of answering them: the first chapter introduces the combination of targeted MS strategies and targeted genetic investigation in knock-out models by means of a highly interesting but analytically challenging compound class: coenzyme Q intermediates. The following chapters all take advantage of the diversity outbred (DO) mouse model to broadly access genetic information via means of quantitative trait loci (QTL) mapping. Chapter 2 explores the genetics of bile acids and cecal lipids in context of the gut microbiome. Bile acids are microbially-derived metabolites recognized for their signaling function in the host. The limitations of this project in sample amounts and large dynamic ranges were circumvented by developing an adapted preparation and targeted analysis method making use of leftover material. The cecal lipids were measured in an untargeted, i. e. discovery way, thus allowing for recognition of unidentified features as molecular actors, one class of which were identified as ornithine lipids. Chapter 3 further develops the idea of utilizing genetic data to guide identification of such unidentified mass spectral features from discovery lipidomics profiling of plasma and liver. Chapter 4 concludes the findings and provides an outlook of expanding this strategy to peptides and features unidentified in a bottom-up proteomics experiment of islets. It further suggests the combination of various MS-based omics technologies in one experiment. Ultimately all scientific research should advance the well-being of our society. Therefore, in line with the Wisconsin idea, Chapter 5 is a summary of this dissertation that makes its science accessible to the wider public.
Post-Election Violence in Kenya: Place-Based Explanations of Conflict
Linke, Andrew M University of Colorado at Boulder 2013 해외박사(DDOD)
When and where do contentious politics become violent politics? How does election violence emerge from, and operate through, formal and informal social institutions? What are the impacts of this electoral violence for the people and places it affects? Focusing on the conflict that followed Kenya's December 27th 2007 national election, I use a geographical conceptual framework and mixed quantitative-qualitative methods to understand a phenomenon that plagues many African societies. I find evidence that local level social circumstances—contextual effects—influence the observed rate of conflict. These settings are measured in terms of ethnic community relations, socioeconomic status, and the institutional legacy of post-independence settlement schemes, among other influences. Overall, I find that local demographic patterns, in terms of prior-incumbency in the national executive and ethnic community polarization (especially in a context of poverty) increase the risk of exposure to electoral violence. There is also evidence that a political economy of insecure land tenure influences the rate of conflict among Kenyan districts, but this relationship holds true mainly in the presence of other contemporary social circumstances. In trying to understand the cyclical nature of political violence, I find that experiences with individual-level election violence reduce several forms of inter-personal and institutional trust, and also affects other social attitudes. There is only mixed evidence that indirect exposure to political violence at a locality scale has additive effects upon individual attitudes. I conclude this research—as I also introduced it—by relating the Kenyan case to other African countries, and in reiterating the important role that localized and place-based social influences have upon electoral political violence.